Sulfinyl Dienes

As we have shown, the sulfinyl group has been widely used as a chiral inductor in Diels-Alder reactions when bonded to the dienophilic double bond, due to its strong ability to control the 7r-facial selectivity. However, only a small number of papers on the use of sulfinyl dienes in asymmetric synthesis have been written, perhaps due to the poor reactivity of many of these substrates and the complex course of their reactions (mainly in the case of 1-sulfinyl dienes, see later). Additionally, the fact that synthetic methods to obtain enantiomerically pure sulfinyl dienes have been available only in the last six years would also explain the low number of papers concerning these asymmetric Diels-Alder reactions. During the preparation of this account, an excellent review on the synthesis and asymmetric Diels-Alder reactions of chiral 1,3-sulfinyl dienes has been published [11]. 

A number of different methods have been used to synthesize racemic sulfinyl dienes. They involve oxidation of dienylthioethers [119], reactions of a-sulfinyl carbanions with different electrophiles [60, 120], sulfoxide-sulfenate rearrangements of propargylic sulfenates followed by isomerization of the resulting sulfinylallenes [121], and reactions of sulfolenes with Grignard reagents [122]. 

From the unequivocally established syn relationship between hydroxy and amino groups in 137, the same relative stereochemistry of the sulfoxide and amino functions in the precursor adducts 136 may be inferred based upon the stereospecific character of the rearrangement. On this basis, it could be concluded that Diels-Alder reaction of sulfinyldiene 134 took place with complete control of endo and regioselectivities. 

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Fernandez de la Pradilla and coworkers167 studied the reactions of chiral sulfinyl and sulfonyl dienes such as 256 and 257 with 7V-phenylmaleimide. They found that the sulfinyl dienes showed facial selectivities opposite to those of the corresponding sulfonyl dienes, indicative of the powerful stereocontrol exerted by the sulfinyl moiety. 

An intermolecular Diels-Alder reaction of the A-sulfinyl diene 116, prepared from amino diene 115, gave a 1 2 mixture of epimers of 1-... 

The synthetic strategies used to prepare optically active sulfinyl dienes (Schemes 67 and 68) differ depending upon the position (C-l or C-2) of the sulfinyl group at the diene. In addition to oxidation of chiral thioethers into the cor-... 

Sulfinyl diene (Rs)-156, derived from (R1,S2,R3) -3-mercaptocamphan-2-ol, reacts with AT-phenylmaleimide [123b] to afford mixtures of two endo adducts 157a and 157b (Scheme 77), with the second as the major product. The 7r-facial selectivity is reversed and become almost complete in the presence of LiCl04 and X2Zn. 

Sulfinyl dienes and vinyl sulfoxides have rarely been used in asymmetric hete-ro-Diels-Alder reactions [145]. The first example was reported in 1992 and describes an intramolecular cycloaddition using a heterodiene bearing a chiral sulfinyl group [146a]. In this paper, the conversion of a-p-tolylsulfinyl a,ft-unsaturated ketone 176 (prepared by Knoevenagel reaction of 3-methylcitronellal and (S)-p-toluenesulfinylacetone) into the hetero-Diels-Alder adducts 177... 

The hetero-Diels-Alder reaction between sulfinyl diene 152a and ethyl gly-oxalate [149] has also been reported. (Scheme 89). In the presence of LiCl04,the endo adducts 185 are predominant, but under Eu(fod)3 or ZnCl2 catalysis the exo adducts 186 are the major ones. The endo/exo selectivity is rather moderate, and the 7r-facial selectivity is low in all cases. 

Discrepancies between different researchers derive from the character inter-or intramolecular of the interactions presumably controlling the reactive conformation. Thus, in most of the cases, the population of the different rotamers in the sulfinylated substrate (only governed by intramolecular interactions) is the only factor considered for explaining the observed 7r-facial selectivity. This explanation (static conformational polarization) was formulated by Koizumi and used by many authors to justify the behavior of vinyl sulfoxides acting as dienophiles and dipolarophiles. A second explanation assumes that the interactions of the two reagents in the transition states determine a different reactivity of the rotamers around the C-S bond. This intermolecular factor can become the most important one in the control of the 7r-facial selectivity of the cycloadditions, and therefore the tendency expected from conformational stability criteria was not observed in those cases where the most reactive conformation is not the most populated one. This dynamic conformational polarization has been used just to explain some of the results obtained for sulfinyl quinones and sulfinyl dienes (unexplainable with the above model) but it can be applied to many other cases. 

The synthesis of electron-deficient diene 285 was achieved by the Stille coupling of P-trifluoromethanesulfonyl-a,P-unsaturated sulfone (284) with a 3-stannyl-a,P-unsaturated ester (283) (Scheme 74).148 Similarly, the preparation of a diverse range of enantiomerically pure 1- and 2-sulfinyl dienes has been achieved via Stille coupling of halovinyl sulfoxides and vinyl stannanes.149,150 Enantiomerically pure 1- and 2-sulfinyl dienes have been used extensively in asymmetric Diels-Alder reactions.111... 

Scheme 64 Diastereomer-dependent lactone formation from cycloadducts involving sulfinylated dienes...

Sulfinyl dienes were made from a,p-unsaturated esters and methyl p-tolyl sulfoxide followed by enolization of the ketone group (eq 16). ... 

Scheme 5.36 Synthesis of sulfinyl diene Fe(0) tricarbonyl complexes.

The reaction of enantiomerically pure sulfinyl dienes with Fe(GO)s yields ( 7" -(lZ)-sulfinyl diene)iron(O) tricarbonyl complexes.Planar and axial chirality are introduced upon complexation of similar ligands with (dba)Fe(GO)3 (dba = dibenzylideneacetone). Gomplexation of sorbic acid with Fe(GO)s in acetone upon irradiation with UV light produced the ( 7" -2,4-hexadienoic acid)Fe(GO)3 complex in good yields.Stobart efal. reported the reaction of 1,4,5,8,9,10-hexahydroanthracene with Fe(GO)s under UV irradiation to form a complex in which two tricarbonyliron moieties are bound in an 77 -fashion to the ends of the isolated conjugated diene units (Equation (8)). 

This methodology appears quite general to synthesize differently substituted conjugate dienes and has been recently applied to the stereoselective synthesis of chiral 2-sulfinylated dienes via the Stille process [171], or nitrogenated dienes via Suzuki [172, 173] or Negishi cross-coupling reactions for instance [174, 175]. 

Eemandez de la Pradilla, R. and Viso, A. (2001) Synthesis of enantiopure tetrahydrofurans from sulfinyl dienes application to the synthesis of (-l-)-trous-kumausyne and (+)-kumausallene. Recent Res. Dev. Org. Bioorg. Chem., 4,123-132. 

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